Erythropoiesis requires a specialised macrophage (MΦ) at the centre of erythroblastic islands (EI). EI MΦ provides iron, growth factors and mediates enucleation of maturing erythroblasts. As macrophages are key effectors of inflammation and innate immunity, we investigated the effect of bacterial LPS in vivo on erythropoiesis and EI MΦ, defined as CD11b+ F4/80+ VCAM1+ CD169+Ly6G+ in mice1. C57BL/6 mice were injected with 2.5 mg/kg/day LPS for 2 days. LPS administration caused a transient whitening of the bone marrow (BM) with decreased numbers of basophilic (9-fold), polychromatic (3.7-fold), orthochromatic erythroblasts (2.2-fold), reticulocytes (2.5-fold) and EI MΦ (7-fold) in the BM. This loss of medullar erythropoiesis was compensated by increased number of EI MΦ (13.6-fold), pro-erythroblasts (1.5-fold), polychromatic (1.9-fold), orthochromatic (3.2-fold) and reticulocytes (2.3-fold) in the spleen. These LPS-mediated responses were abrogated in TLR4 KO mice demonstrating that erythropoiesis and EI MΦ suppression in response to LPS are TLR4-dependant. As G-CSF treatment results in similar suppression of erythropoiesis1, we examined whether the mechanism could be indirect via endogenous G-CSF release. LPS induced a transient 80-fold increase in G-CSF concentration in the blood. When LPS was administered to G-CSF receptor (GCSFR) KO mice, medullar erythropoiesis was still suppressed in GSFR KO mice despite high numbers of mature erythrocytes, and normal numbers of EI MΦ in the BM. To understand how BM erythrocytes could be increased whilst erythropoiesis was suppressed in LPS-treated GCSFR KO mice, we measured vascular leakage. Blood plasma/femur volume in the BM of LPS-treated GCSFR KO mice was 2.9-fold higher compared to LPS-treated wild-type mice, explaining the high content in BM erythrocytes despite suppressed erythropoiesis and also suggesting that GCSFR-mediated signaling is necessary to maintain the integrity of the BM vasculature in response to LPS. In conclusion LPS-mediated medullar erythropoiesis suppression is TLR4-dependent and involves GCSFR-dependent and independent mechanisms.